A large-scale cohort study found that maternal influenza infection during pregnancy may be associated with a slightly increased risk of childhood seizures, particularly febrile seizures, in offspring.

In the study, published in JAMA Network Open, investigators analyzed the data of over 1.3 million mother-offspring pairs between 2004 and 2013. They identified 75,835 mothers who had influenza during pregnancy and matched them 1:4 with 303,340 control mothers without influenza.

The study utilized Taiwan's comprehensive Maternal and Child Health Database, which links several national health datasets. Mother-offspring pairs were followed until December 2020, providing up to 16 years of follow-up data. Influenza infection was identified using ICD-9-CM and ICD-10-CM codes from medical records.

Among the key findings were:

• Among 75,835 offspring exposed to maternal influenza, 2,456 (3.2%) of them developed seizures during follow-up.
• The cumulative risk of seizures and febrile convulsions was significantly higher in the influenza group.
• No statistically significant differences were observed between trimesters regarding the timing of influenza infection.
• Placenta previa or abruption was slightly more prevalent in the influenza group (1.6% vs 1.4%, P < .001).

After adjusting for potential confounders, the offspring of mothers with influenza had a 9% higher risk of seizures overall (adjusted hazard ratio [HR] = 1.09, 95% confidence interval [CI] = 1.05–1.14) and an 11% higher risk of febrile seizures specifically (adjusted HR = 1.11, 95% CI = 1.06–1.17) compared with controls. No significant association was found for epilepsy (adjusted HR = 1.04, 95% CI = 0.97–1.13).

Additional data from the study revealed:

• The predominant maternal age group was 25 to 29 years in both influenza and control groups.
• Male offspring comprised 51.9% of both groups.
• Cesarean delivery rates were 36.7% in the influenza group and 33.8% in the control group.
• Low birth weight (< 2,500g) occurred in 6.8% of the influenza group and 7.2% of the control group.
• Preterm birth (< 37 weeks) rates were 7.8% in the influenza group and 7.9% in the control group.

The study controlled for various maternal factors, including age, family income, urbanization, pregnancy-related complications, mode of delivery, offspring sex, multiple births, birth weight, and gestational age. Male offspring sex (adjusted HR = 1.28, 95% CI = 1.23–1.32), cesarean delivery (adjusted HR = 1.09, 95% CI = 1.05–1.14), low birth weight (2,000-2,499 g vs ≥ 2,500 g: adjusted HR = 1.27, 95% CI = 1.17–1.38), and preterm birth (32 to 36 weeks vs ≥ 37 weeks: adjusted HR = 1.23, 95% CI = 1.14–1.33) were associated with increased seizure risk.

Limitations included potential misclassification of influenza exposure and outcomes caused by reliance on ICD codes, lack of data on influenza vaccination and antiviral medication use, and unavailable information on offspring lost to follow-up.

The investigators noted that maternal immune activation and placental inflammation may play a role in fetal neurodevelopmental outcomes. They suggested that cytokine storms induced by maternal influenza infection could be a possible pathogenetic mechanism.

The authors declared having no competing interests.